A 3D tension bioreactor platform to study the interplay between ECM stiffness and tumor phenotype.
A 3D tension bioreactor platform to study the interplay between ECM stiffness and tumor phenotype.
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DOI：
10.1016/j.jbiotec.2014.11.008
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发表时间：
2015-01-10
影响因子：
4.1
通讯作者：
Weaver, Valerie M.
中科院分区：
文献类型：
--
作者：
Cassereau, Luke;Miroshnikova, Yekaterina A.;Ou, Guanqing;Lakins, Johnathon;Weaver, Valerie M.
细胞外基质 (ECM) 结构、组成和硬度对组织发育和心血管疾病和癌症等病理学具有深远影响。因此，人们设计了多种合成水凝胶系统来研究 ECM 成分、密度、力学和形貌对细胞和组织表型的影响。然而，这些合成系统无法准确概括天然组织 ECM 的生物学特性和结构。天然三维 (3D) ECM 水凝胶，例如胶原蛋白或透明质酸，具有组织的许多化学和物理特性，但这些系统具有局限性，包括无法独立控制生物物理特性，例如刚度和孔径。在这里，我们提出了一种 3D 张力生物反应器系统，该系统可以精确机械调节胶原水凝胶的硬度，同时保持一致的成分和孔径。我们通过机械加载与聚二甲基硅氧烷（PDMS）膜共价结合的胶原水凝胶以诱导水凝胶硬化来实现这一目标。我们验证了该系统的生物学应用，将致癌转化的乳腺上皮细胞类器官嵌入 3D I 型胶原蛋白水凝胶中，均匀硬化或校准以创建 ECM 硬化梯度，以直观地展示 ECM 硬化对转化和肿瘤细胞侵袭的影响。因此，该生物反应器提出了第一个可调谐 3D 天然水凝胶系统，能够独立评估 ECM 硬度对组织表型的作用。
Extracellular matrix (ECM) structure, composition, and stiffness have profound effects on tissue development and pathologies such as cardiovascular disease and cancer. Accordingly, a variety of synthetic hydrogel systems have been designed to study the impact of ECM composition, density, mechanics, and topography on cell and tissue phenotype. However, these synthetic systems fail to accurately recapitulate the biological properties and structure of the native tissue ECM. Natural three dimensional (3D) ECM hydrogels, such as collagen or hyaluronic acid, feature many of the chemical and physical properties of tissue, yet, these systems have limitations including the inability to independently control biophysical properties such as stiffness and pore size. Here, we present a 3D tension bioreactor system that permits precise mechanical tuning of collagen hydrogel stiffness, while maintaining consistent composition and pore size. We achieve this by mechanically loading collagen hydrogels covalently-conjugated to a polydimethylsiloxane (PDMS) membrane to induce hydrogel stiffening. We validated the biological application of this system with oncogenically transformed mammary epithelial cell organoids embedded in a 3D collagen I hydrogel, either uniformly stiffened or calibrated to create a gradient of ECM stiffening, to visually demonstrate the impact of ECM stiffening on transformation and tumor cell invasion. As such, this bioreactor presents the first tunable 3D natural hydrogel system that is capable of independently assessing the role of ECM stiffness on tissue phenotype.
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影响因子：
14
作者：
Wipff, Pierre-Jean;Majd, Hicham;Hinz, Boris
通讯作者：
Hinz, Boris
DOI：
10.1039/c1ib00043h
发表时间：
2011-09
期刊：
Integrative biology : quantitative biosciences from nano to macro
影响因子：
--
作者：
Lopez JI;Kang I;You WK;McDonald DM;Weaver VM
通讯作者：
Weaver VM
影响因子：
14
作者：
Young, Jennifer L.;Engler, Adam J.
通讯作者：
Engler, Adam J.
影响因子：
2
作者：
Miroshnikova YA;Jorgens DM;Spirio L;Auer M;Sarang-Sieminski AL;Weaver VM
通讯作者：
Weaver VM
影响因子：
8
作者：
Provenzano, P. P.;Inman, D. R.;Eliceiri, K. W.;Keely, P. J.
通讯作者：
Keely, P. J.